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A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IMC-A12
Mitoxantrone
Prednisone
IMC-1121B (ramucirumab)
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • The participant has histologically-confirmed adenocarcinoma of the prostate
  • The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)
  • The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)
  • The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

  • The participant must have evidence of progressive disease defined as at least one of the following;

    1. Progressive measurable disease: using conventional solid tumor criteria
    2. Bone scan progression: at least two new lesions on bone scan
    3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2
  • The participant has a PSA ≥ 2 ng/mL
  • The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment
  • The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
  • The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)
  • The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)
  • The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)
  • The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
  • The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a Partial Thromboplastin Time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)
  • The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

  • The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)
  • The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)
  • The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN
  • The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab
  • The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration
  • The participant has known or suspected brain or leptomeningeal metastases
  • The participant has uncontrolled or poorly controlled hypertension
  • The participant has poorly controlled diabetes mellitus. Inclusion Criteria:
  • The participant has histologically-confirmed adenocarcinoma of the prostate
  • The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)
  • The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)
  • The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

  • The participant must have evidence of progressive disease defined as at least one of the following;

    1. Progressive measurable disease: using conventional solid tumor criteria
    2. Bone scan progression: at least two new lesions on bone scan
    3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2
  • The participant has a PSA ≥ 2 ng/mL
  • The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment
  • The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
  • The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)
  • The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)
  • The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)
  • The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
  • The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)
  • The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

  • The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)
  • The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)
  • The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN
  • The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab
  • The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration
  • The participant has known or suspected brain or leptomeningeal metastases
  • The participant has uncontrolled or poorly controlled hypertension
  • The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
  • The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
  • The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

Sites / Locations

  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
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  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
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  • ImClone Investigational Site
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  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
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  • ImClone Investigational Site
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  • ImClone Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone

IMC-A12 + Mitoxantrone + Prednisone

Arm Description

Outcomes

Primary Outcome Measures

Composite Progression-free Survival (cPFS)
Defined as the median time from randomization to the earliest of: Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of >=2 new lesions; New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression) Symptomatic progression (for participants without measurable disease); Other clinical events attributable to prostate cancer that require major interventions; or Death from any cause Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.

Secondary Outcome Measures

Summary Listing of Participants Reporting Treatment-Emergent Adverse Events
Data presented are the number of participants who experienced A12 or 1121B (ramucirumab) related treatment-emergent adverse events (TEAE), treatment related serious adverse events (SAE), or any Grade 3 or higher TEAE; any TEAE leading to discontinuation of A12 or 1121B (ramucirumab) treatment, and any TEAE leading to dose modification of A12 or 1121B (ramucirumab). A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Event section.
Time to Radiographic Evidence of Disease Progression
Time between date of randomization and earliest date of radiographic progression defined as either: Tumor progression by RECIST; Evidence of progression by bone scan; New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression). Participants who were ongoing with no radiographic evidence of disease progression, who discontinued treatment for reasons other than progression,or died before progression were censored at date of last tumor or bone radiographic assessment. Participants who started a new anticancer treatment before progression were censored at date of last tumor or bone radiographic assessment before start of new anti-cancer therapy.
Prostate Specific Antigen (PSA) Response Rate
PSA response rate is defined as the percentage of participants with a decrease in PSA >= 50 percent from baseline.
Composite Progression-free Survival (cPFS) at 6-months
Data presented are the percentage of participants without disease progression at 6 months. Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Composite Progression-free Survival (cPFS) at 9-months
Data presented are the percentage of participants without disease progression at 9 months. Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Composite Progression-free Survival (cPFS) at 12-months
Data presented are the percentage of participants without disease progression at 12 months. Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Overall Survival (OS)
Overall survival is defined as the time from randomization to the date of death due to any cause. Participants who were alive at the time of study completion were censored at the time the participant was last known to be alive.
Objective Response Rate (ORR)
Objective response is Complete Response (CR) + Partial Response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is a disappearance of all target and non-target lesions; PR is at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.
Maximum Concentration (Cmax) at Study Day 1
Maximum Concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Maximum Concentration (Cmax) at Study Day 15
Maximum concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Maximum Concentration (Cmax) at Study Day 16
Maximum concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Maximum Concentration (Cmax) at Study Day 30
Maximum concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Minimum Concentration (Cmin) at Study Day 1
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Minimum Concentration (Cmin) at Study Day 15
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Minimum Concentration (Cmin) at Study Day 16
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Minimum Concentration (Cmin) at Study Day 30
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Full Information

First Posted
May 19, 2008
Last Updated
October 7, 2014
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00683475
Brief Title
A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer
Official Title
A Phase 2, Multicenter, Randomized Study of IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer (AIPC) Following Disease Progression on Docetaxel-Based Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether IMC-A12 or IMC-1121B (ramucirumab) with Mitoxantrone and Prednisone is effective in the treatment of metastatic androgen- independent prostate cancer (APIC).
Detailed Description
Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-related death in men in the United States. Chemotherapy, either as a single agent or in combination, may lead to clinical response, pain control, and/or improved quality of life. Docetaxel is now the first-line standard therapy for AIPC. Mitoxantrone was approved in 1996 for use in combination with corticosteroids as initial chemotherapy for pain related to advanced Hormone Refractory Prostate Cancer (HRPC). Hormonal manipulations and docetaxel-based chemotherapy are often effective in metastatic prostate cancer; however, disease becomes refractory to these interventions in the majority of men. Although mitoxantrone continues to be a significant agent in the treatment of HRPC, there exists a need for more efficacious therapy in docetaxel-refractory- AIPC. Because of the potential contribution of Insulin Like Growth Factor Receptor (IGF-IR) and VEGFR-2 mediated pathways in prostate cancer pathogenesis, it is hypothesized that each of these biological agents in combination with mitoxantrone and prednisone will result in clinically meaningful activity in AIPC. Therefore, ImClone plans to conduct a randomized Phase 2 trial to assess the safety and efficacy of IMC-A12 or IMC-1121B (ramucirumab) in combination with mitoxantrone and prednisone in participants with AIPC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
138 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone
Arm Type
Experimental
Arm Title
IMC-A12 + Mitoxantrone + Prednisone
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
IMC-A12
Other Intervention Name(s)
cixutumumab, LY3012217
Intervention Description
IMC-A12 is to be administered as an I.V. infusion, 6 mg/kg over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. IMC-A12 treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Intervention Description
Mitoxantrone is to be administered as an I.V. infusion, at 12 milligrams/square meter (mg/m^2) over 5-15 minutes on Day 1 during a 3-week (21-day) cycle. Mitoxantrone treatment is to be continued for a maximum of 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤ 144 mg/m^2) or until there is evidence of disease progression, death, or intolerable toxicity.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.
Intervention Type
Biological
Intervention Name(s)
IMC-1121B (ramucirumab)
Other Intervention Name(s)
ramucirumab, IMC-1121B, LY3009806
Intervention Description
IMC-1121B (ramucirumab) is to be administered as an intravenous (IV) infusion, 6 milligrams/kilogram (mg/kg) over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. Ramucirumab treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.
Primary Outcome Measure Information:
Title
Composite Progression-free Survival (cPFS)
Description
Defined as the median time from randomization to the earliest of: Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of >=2 new lesions; New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression) Symptomatic progression (for participants without measurable disease); Other clinical events attributable to prostate cancer that require major interventions; or Death from any cause Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Time Frame
Randomization to composite progressive disease, up to 23.4 months
Secondary Outcome Measure Information:
Title
Summary Listing of Participants Reporting Treatment-Emergent Adverse Events
Description
Data presented are the number of participants who experienced A12 or 1121B (ramucirumab) related treatment-emergent adverse events (TEAE), treatment related serious adverse events (SAE), or any Grade 3 or higher TEAE; any TEAE leading to discontinuation of A12 or 1121B (ramucirumab) treatment, and any TEAE leading to dose modification of A12 or 1121B (ramucirumab). A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Event section.
Time Frame
Randomization to 36.3 months
Title
Time to Radiographic Evidence of Disease Progression
Description
Time between date of randomization and earliest date of radiographic progression defined as either: Tumor progression by RECIST; Evidence of progression by bone scan; New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression). Participants who were ongoing with no radiographic evidence of disease progression, who discontinued treatment for reasons other than progression,or died before progression were censored at date of last tumor or bone radiographic assessment. Participants who started a new anticancer treatment before progression were censored at date of last tumor or bone radiographic assessment before start of new anti-cancer therapy.
Time Frame
Randomization to date of radiographic progression, up to 36.3 months
Title
Prostate Specific Antigen (PSA) Response Rate
Description
PSA response rate is defined as the percentage of participants with a decrease in PSA >= 50 percent from baseline.
Time Frame
Baseline up to data cut-off date (up to 36.3 months)
Title
Composite Progression-free Survival (cPFS) at 6-months
Description
Data presented are the percentage of participants without disease progression at 6 months. Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Time Frame
6 months
Title
Composite Progression-free Survival (cPFS) at 9-months
Description
Data presented are the percentage of participants without disease progression at 9 months. Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Time Frame
9 months
Title
Composite Progression-free Survival (cPFS) at 12-months
Description
Data presented are the percentage of participants without disease progression at 12 months. Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
Time Frame
12 months
Title
Overall Survival (OS)
Description
Overall survival is defined as the time from randomization to the date of death due to any cause. Participants who were alive at the time of study completion were censored at the time the participant was last known to be alive.
Time Frame
First dose to death due to any cause up to 36.3 months
Title
Objective Response Rate (ORR)
Description
Objective response is Complete Response (CR) + Partial Response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is a disappearance of all target and non-target lesions; PR is at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.
Time Frame
Baseline to date of progressive disease or death up to 36.3 months
Title
Maximum Concentration (Cmax) at Study Day 1
Description
Maximum Concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 1
Title
Maximum Concentration (Cmax) at Study Day 15
Description
Maximum concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 15
Title
Maximum Concentration (Cmax) at Study Day 16
Description
Maximum concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 16
Title
Maximum Concentration (Cmax) at Study Day 30
Description
Maximum concentration (Cmax) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 30
Title
Minimum Concentration (Cmin) at Study Day 1
Description
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 1
Title
Minimum Concentration (Cmin) at Study Day 15
Description
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 15
Title
Minimum Concentration (Cmin) at Study Day 16
Description
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 16
Title
Minimum Concentration (Cmin) at Study Day 30
Description
Minimum concentration (Cmin) of Ramucirumab. All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.
Time Frame
Day 30

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The participant has histologically-confirmed adenocarcinoma of the prostate The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2) The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent) The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent The participant must have evidence of progressive disease defined as at least one of the following; Progressive measurable disease: using conventional solid tumor criteria Bone scan progression: at least two new lesions on bone scan Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2 The participant has a PSA ≥ 2 ng/mL The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL) The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present) The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min) The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a Partial Thromboplastin Time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3) The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN Exclusion Criteria: The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.) The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted) The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration The participant has known or suspected brain or leptomeningeal metastases The participant has uncontrolled or poorly controlled hypertension The participant has poorly controlled diabetes mellitus. Inclusion Criteria: The participant has histologically-confirmed adenocarcinoma of the prostate The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2) The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent) The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent The participant must have evidence of progressive disease defined as at least one of the following; Progressive measurable disease: using conventional solid tumor criteria Bone scan progression: at least two new lesions on bone scan Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2 The participant has a PSA ≥ 2 ng/mL The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL) The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present) The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min) The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3) The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN Exclusion Criteria: The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.) The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted) The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration The participant has known or suspected brain or leptomeningeal metastases The participant has uncontrolled or poorly controlled hypertension The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
ImClone Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
ImClone Investigational Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
ImClone Investigational Site
City
Port St. Lucie
State/Province
Florida
ZIP/Postal Code
34952
Country
United States
Facility Name
ImClone Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
ImClone Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
ImClone Investigational Site
City
Chlcago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
ImClone Investigational Site
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
ImClone Investigational Site
City
Maryville
State/Province
Illinois
ZIP/Postal Code
62062
Country
United States
Facility Name
ImClone Investigational Site
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52402
Country
United States
Facility Name
ImClone Investigational Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
ImClone Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
ImClone Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
ImClone Investigational Site
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
ImClone Investigational Site
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
ImClone Investigational Site
City
Roseland
State/Province
New Jersey
ZIP/Postal Code
07068
Country
United States
Facility Name
ImClone Investigational Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
ImClone Investigational Site
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
ImClone Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
ImClone Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
ImClone Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
ImClone Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
ImClone Investigational Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
ImClone Investigational Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
ImClone Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
ImClone Investigational Site
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
ImClone Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
ImClone Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
ImClone Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
ImClone Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
ImClone Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
ImClone Investigational Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26082390
Citation
Hussain M, Rathkopf D, Liu G, Armstrong A, Kelly WK, Ferrari A, Hainsworth J, Joshi A, Hozak RR, Yang L, Schwartz JD, Higano CS. A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer. Eur J Cancer. 2015 Sep;51(13):1714-24. doi: 10.1016/j.ejca.2015.05.019. Epub 2015 Jun 13.
Results Reference
derived

Learn more about this trial

A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer

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